The present invention relates to prevention of intraabdominal infections and especially to prevention of infections associated with indwelling catheters.
Although certain abdominal cavities are typically low in bacteria count and are classified as infection free, the use of conventional intra-abdominal instrumentation, such as catheters, in these cavities is often accompanied by a large number of infections (that is, a high relative bacteria count). Of such infections, those of the urinary tract are the most common, accounting for as many as forty percent of all nosocomial infections. A nosocomial infection is an infection acquired during hospitalization which was not present or incubating when the patient was admitted to the hospital. The majority of urinary tract infections are associated with indwelling urethral catheters or other types of urethra and bladder penetrating instrumentation. Infections resulting from urinary catheters have been responsible for excess mortality as well as morbidity among the catherized population and have been the subject of numerous, and most often at least partly unsuccessful, attempts to control or prevent same.
The potential sequelae of such urinary tract infections include: gram-negative rod bacteremia; anti-microbial toxicity during treatment; acute and chronic pyelonephritis; chronic bactiuria; perinephric, vesical and urethral abscesses; bladder and renal stones; bladder cancer; renal failure and death. These complications result in substantially increased costs for treatment.
The uninstrumented bladder is usually sterile or very low in bacteria count. Passage of a catheter through the urethra offers a portal for organisms that may overwhelm the bladder's defenses. One source of urethral organisms are those organisms that are carried into the bladder by insertion of the catheter. Catheters not removed immediately but left indwelling offer additional opportunities for entry of bacteria. A frequent source for the infecting organisms is endogenous from the patient's own fecal or urethral flora. Once these organisms are in the periurethral area they may travel into the bladder between the urethral mucosae and the external catheter surface. An additional source for the infection is exogenous contamination by hospital personnel at the junction of the catheter and the collecting tube or drain hose on the collecting bag. Thus, attempts to disinfect the collecting bag reduce but do not eliminate these nosocomial infections, especially since the infections are more frequent in women apparently due to contamination of the periurethral area.
None of the prior art catheters and methods have been fully successful in preventing or controlling the urinary tract infections associated with such catheters.
There follows a general outline of some of the attempts that have been made at preventing infections resulting from catheterization, especially bladder infections.
As early as 1928 certain physicians and theorists advocated closed drainage catheter systems, that is a collection bag is connected to a drainage tube associated therewith in a sealed or fused manner to prevent breaking into the tube and thereby allowing bacteria or other microorganisms to gain entry into the interior of the catheter and from there to migrate to the bladder. The closed drainage systems did not become widespread until the early 1960's. The incidence of bactiuria is substantially lower in closed systems as compared to open systems, however, infections do still occur. A more recent closed system concept includes a technique wherein the catheter is taped to the collecting tube so that it can be visually determined if the junction has been inadvertently opened, that is the tape is broken, and steps can be taken to correct the problem.
Antibiotics have also been frequently utilized as a prophylaxis to infection in the bladder occasioned by catheterization. In particular, antibiotics are given to catheterized patients at or prior to catheterization and continuing while the patient is catheterized and before the actual development of urinary tract infections so as to prevent or postpone an infection. Careful analysis of data from such treatments suggests that the use of antibiotics may result in lower rates of infection and fewer febrile episodes in catherized patients. However, serious disadvantages associated with the use of antibiotics include allergic or toxic reactions to the antibiotic, selective increases in resistant organisms and increased cost. In particular, strains of microorganisms which are resistant to the particular antibiotics may multiply as well or even better than if no antibiotic were used.
Antibiotic treatment has also been utilized to treat organisms once infection has taken place. When the catheter is to remain indwelling for a long period of time, such treatment is normally not successful for the patient will become infected again after an initial infection has been controlled. If the catheter is to be removed within seventy-two hours, it is generally accepted that such treatment will probably be successful with the limitations and hazards of prophylactic antibiotics, provided that an appropriate antibiotic is chosen which is effective against the particular infecting microorganism.
Another type of treatment has been directed to preventing microorganisms from entering the urethra and migrating to the bladder outside the catheter. Such treatments often include the use of antiseptic ointments such as polymycin B or organically complexed iodine solutions such as are marketed under the name Betadine. Application of an ointment to the periurethral space or on the outside of the catheter at the time of catheterization will often delay the development of nosocomial urinary tract infection; however, daily application of an ointment to the urethra and external region surrounding the catheter, once the catheter is in place, is normally detrimental rather than preventive and often results in an increased incidence of infections.
Intermittent catheterization is a technique which has been used most successfully in patients with neurogenic bladders. In this technique a small bore catheter is inserted 3 times daily. This is not practical in a hospital population due to the substantial amount of time required to effect each catheterization.
Another method utilized in the past has been to have a potential bladder infection patient ingest urine acidifying agents, such as mandelamine. The mendelamine is metabilized to formaldehyde in the kidney which then enters the bladder and lowers the urine pH to less than 6.0. This treatment has been most successful in preventing recurrent infections in a non-catheterized patient population. Such treatment often fails in catheterized patients because there is inadequate retention time in the bladder to retain formaldehyde in the bladder which is continuously draining.
Various types of bladder irrigations have been attempted to prevent or eliminate infection accompanying catheterization. Bladder irrigation with antimicrobial agents is probably the most widely practiced attempt to prevent urinary tract infection subsequent to catheterization. Since entry of bacteria was not preventable in the early techniques wherein the catheter systems were open, it was postulated that an irrigation with antimicrobial solutions would prevent multiplication of organisms and possibly the development of bacteriuria. Irrigation in open systems by continuous and intermittent methods have both been used. An intermittent irrigation often included the addition of a solution including the antimicrobial agent into the bladder through the catheter drainage lumen. The lumen was then clamped and the solution retained for a short time. This technique was used for prevention of bacterial infection in patients with indwelling urinary catheters and those receiving intermittent catheterization. This method was not greatly effective in preventing bactiuria.
A continuous irrigation system, using an indwelling triple-lumen catheter, was originally designed to allow continuous flushing and to thereby prevent obstruction of the catheter by blood clots following surgery of the genitourinary tract. For prevention of infection, an antimicrobial solution was dripped into the inlet port of the catheter and drained through a second lumen. The third lumen is for inflation of the balloon at the tip of the catheter which secures proper placement. This system allows continuous flow of the flushing or irrigant solution into the bladder. With this system, contact of the bladder with the irrigant is restricted to the area surrounding the catheter tip. Unless the antimicrobial solution comes in contact with the entire bladder mucosae this therapy will fail to prevent urinary tract infections in the untreated areas.
Various other attempts have been made to design a catheter structure that will actively or passively prevent bladder infections. For example, certain structures have been designed to facilitate the drainage of urine from the bladder. Other catheters are designed to irrigate the periurethral area, especially the bladder and to empty directly into a drainage lumen so as not to expand the bladder with irrigating fluid such that the bladder mucosae is entirely directly exposed to the fluid during the irrigation.
Another catheter designed to overcome infection comprises a silver rod which slowly releases silver within the bladder to kill organisms through action of silver. This treatment only selectively kills certain organisms not resistant to oligodynamic action, is bacteriostatic rather than bacteriocidal and is expensive.
In general, multilumen catheters have previously been developed for continuous irrigation of the bladder. However, these catheters have not been entirely successful, theoretically for several reasons. First, continuous irrigation, as was mentioned above, has not resulted in a thorough exposure of the bladder wall to the antiseptic, or antibiotic in the irrigating solution. Secondly, the opening of the catheter system to the environment as required for routine maintenance during continuous irrigation may allow bacteria into the catheter system, thus counteracting any positive effects resulting from the continuous irrigation itself. In fact, reinfection may make continuous irrigation less effective than no irrigation at all. Thirdly, the irrigants used have been of questionable effectiveness in preventing or eliminating the infections, which result from a wide variety of bacteria species and other microorganisms.
Tidal drainage irrigation techniques, where the outflow line is clamped until the bladder has reached a physiologic volume (about two hours at an irrigant flow rate of one milliliter per minute), increases contact time and the distribution of the irrigant. Painful bladder contraction that may occur with some types of irrigation can be prevented with tidal drainage. However, the narrow outflow lumen in the three-way catheter is susceptible to clogging and, despite the increased effluent flow, may require disconnection of the closed system to clear an obstruction. Such opening of the closed system allows entry of microorganisms and is considered undesirable.
Various techniques utilizing intermittent irrigations have also been utilized to lower the incidence of bladder infections in catheterized patients. For example, addition of a neomycin solution following catheterization was tried but found to have little or no effect on decreasing the incidence or urinary tract infections. Furthermore, a greater percentage of infections related to more resistant pathogens was seen in patients receiving neomycin irrigations. In particular, there was an increase in the number of infections by Pseudomonas aeruginosa and Group D streptococci (Enterococcus).
In single catheterizations irrigation by chlorhexidine digluconate (0.02%) has been found to be somewhat effective in reducing the incidence of infections. Also, in patients with existing infections, irrigation twice daily with chlorhexidine digluconate (0.02%) will decrease bacterial counts in the urine but has not been found to sterilize the urine. Thus, such treatment is not recommended for existing urinary tract infections. A 4% solution of such chlorhexidine is required for immediate bacteriocidal effect but solutions that are greater than 0.02% tend to be irritating to the bladder.
Acetic Acid (0.025%) is probably the most frequently used conventional intermittent irrigation solution. It is effective in decreasing debris. However, controlled studies using acetic acid as an irritant have failed to show decreased bacterial counts in patients with indwelling catheters.
Silver nitrate has also been tested as a intermittent irrigation. The patients of the tests were asked to retain the solution for thirty minutes for complete batericidal action. The solution caused severe pain and the maximum time a patient could retain the silver nitrate in the bladder was two minutes.
Further, polyvinylpyrrolidone-Iodine (10%) solution has been used in experimental animals as a bladder irrigant to prevent infections. A moderate to severe erosive cystitis occurred in all animals suggesting that such therapy would not be useable in humans.
In open catheter systems continuous antimicrobial bladder irrigations have been somewhat effective in decreasing the overall rate of urinary tract infection. Both continuous acetic acid at 0.25% and neomycin/polymyxin B irrigations have also been somewhat effective in delaying the onset of bacteriuria in open catheter systems. Continuous irrigation with nitrofurazone has been utilized but has been shown to be inferior to neomycin/polymyxin B in preventing bacteriuria in catheterized patients, and produced a significant incidence of hematunia and is not recommended for use because of its relative ineffectiveness and substantial toxicity.
In closed catheter sytems, continuous antimicrobial irrigations have not been demonstrated to decrease the incidence of urinary tract infection. Irrigations with either neomycin alone or in combination with polymyxin B have not significantly altered the rates at which bacteriuria occurs. Chlorhexidine solution administered by continuous irrigation has not been shown to be an improvement over no irrigation.
Continuous bladder irrigations for eradication of existing infections have been of limited value or no value. Irrigation of an open catheter system with neomycin/polymyxin B has been found to be ineffective in sterilizing the urine, although most infecting organisms were sensitive to the antibiotics. In fact, superinfection with resistant organisms occured in most cases. In patients with severe fungal cystitis or fungus balls limited to the lower urinary tract, continuous irrigation with Amphotericin B is effective but Amphotericin B is not effective against bacteria.
In the process of inhibiting a portion of the organisms from gaining entry into a catheterized system, antimicrobial irrigations exert a selective pressure which increases frequency of resistant organism such as Entemococcus, Pseudomonas, Proteus and Caudiat.
There has not been found conclusive evidence in the medical literature that prophylatic irrigations with any solution will decrease urinary tract infection rates in closed catheter drainage system. Prophylatic irrigations seem to be ineffective and may be a predisposing factor toward contamination of the system and subsequent urinary tract infections.
Therefore, the conventional methods involving continuous irrigation of an abdominal cavity to control infection have been ineffective. In addition, other problems have been associated with the previous methods. First, the equipment necessary to maintain a continuous irrigation is cumbersome and restricts patient mobility and comfort. Secondly, continuous irrigation equipment requires frequent monitoring by health services personnel to ensure proper irrigation. Thirdly, the prior art irrigation equipment is subject to patient tampering causing both reinfection problems and potential blockage of the fluid so as to prevent drainage. Fourthly, prior art continuous irrigation does not readily allow for the occasional treatment of the patient's abdominal cavity with medications such as an anesthetic to control spasms and maximize patient comfort. And fifthly, prior art continuous irrigation equipment is not readily adapted for treatment of other troublesome infections of the abdominal cavity (such as from cystoscopies, cystitis, and, in particular, pyocystitis).
Another problem associated with previous attempts to prevent urinary tract infections has been that a totally satisfactory solution for killing and preventing growth of microorganisms was not recognized. Various solutions were used with varying effects. For instance, use of an antibiotic solution, as previously discussed, often resulted in prevention of some bacterial growth when the bacteria was effected by the antibiotic; however, other resistant bacteria will be immune to a particular antibiotic and these continue to grow. Also yeast and certain other non-bacteria microorganisms are normally not affected by antibiotics.
Other attempts to find a suitable solution or irrigant to make abdominal cavities antiseptic, especially the bladder, have not been satisfactory as some of the irrigants, silver nitrate for example, are very effective in killing microorganisms, but are too painful and irritating to the patient for routine use. Other irrigants, while effective in killing microorganisms are harmful or deadly to tissue or cannot be used internally for reasons of toxicity. For instance, some of the organic chlorides are toxic. Attempts have been specifically made to try to use standard povidone-iodine solutions as irrigants; however, such solutions have often resulted in severe problems. For example, studies on rats suggest that povidone-iodine irrigations may cause erosive cystitis. Theoretically, the problem with povidone solutions, and other organic iodine complexing compounds, is that, for example, a standard 10% povidone solution has about 10,000 parts per million (by weight) complexed iodine and about one part per million free iodine (depending on temperature, etc.) Solutions of one part per million free iodine should be nontoxic; however, there is a relatively fast working chemical equilibrium function in the povidone solutions which replaces the free iodine almost immediately upon its use. Therefore, the entire 10,000 parts per million of complexed iodine in such a solution are readily and quickly available as free iodine. A solution having 10,000 parts per million of free iodine can cause serious tissue damage and may be fatal if used internally in a human. Also, the povidone may cause decomposition of catheters used in conjunction with the irrigant. Other previously discussed solutions such as acetic acid and neomycin/polymyxin B solutions have been shown ineffective in killing bladder infection in catheterized patients. As a result of the previous problems, the prior art does not disclose the use of an unquestionably safe, effective irrigant in bladder irrigation.
Certain particular problems with infection occurs in other parts of the abdominal cavity. For example, peritonitis is one of the commonest complications of peritoneal dialysis. As many as 46% of patients undergoing dialysis have been shown to have an occurance of peritonitis before the end of the first year of treatment. Attempts at prevention of peritonitis have been unsuccessful, thus leaving infection a major threat to dialysis patients.
Similar problems persist in colon surgery. Although infection is not a problem in the normal colon, when the colon wall is disturbed during surgery, infection may set in. The prior art does not disclose an effective method of preventing such infection.
Accordingly, in order to stop the proliferation of infections in abdominal cavities, especially due to instrumentation such as catheterization, a previously unsatisfied need exists for an effective method of control of intra-abdominal cavity infections, and a catheter device adapted to implement such a method of treatment.